A state of immunosuppression of a host is often an undesired side effect of drug treatment; such an effect is commonly found as the result of cancer chemotherapy involving antineoplastic agents. Such a suppression of the immune system lessens the body's own natural defense mechanisms and enhances the probability of infection.
As used herein, an immunomodulator is an agent which enhances a depressed immune function of a host mammal. Immune function is defined as the development and expression of humoral (antibody-mediated) immunity, cellular (t-cell-mediated) immunity, or macrophage and granulocyte mediated resistance. It includes agents acting directly on the cells involved in the expression of immune response, or on cellular or molecular mechanisms which act to modify the function of cells involved in immune response. Augmentation of immune function may result from the action of an agent to abrogate suppressive mechanisms by negative-feedback influences endogenous or exogenous to the immune system. Thus, immunomodulators have diverse mechanisms of action. Despite the diversity of cell site of action and biochemical mechanism of action of immunomodulators, their applications are essentially the same; that is, to enhance host resistance.
The principal protective function of the immune system relates to resistance to invasion by pathogens, including viruses, rickettsia, mycoplasma, bacteria, fungi and parasites of all types. Thus, improvement of immune response, particularly when depressed, would be expected to improve resistance to infection or infestation by any of the above pathogens. An immunomodulator alone or in combination with anti-infective therapy can be applied to any and all infectious diseases.
Another protective function of the immune system is thought to be resistance to malignant cell development as in cancer. The use of immunomodulators can be used in cancer treatment to enhance tumor rejection and to inhibit tumor recurrences following other forms of therapy.
Each of the protective functions of the immune system can be modified by therapy with immunomodulators alone or in combination with other agents employed to improve resistance or to kill the invading pathogen. In addition, specific resistance can be augmented by use of immunomodulators in conjunction with some form of antigen as in a vaccine employing, for example, virus, tumor cells, etc. This could induce specific immunity or tolerance. Use of immunomodulators may be either therapeutic or prophylactic; the latter particularly in aging where infection and cancer are more common, or where immunosuppression is induced by drugs, trauma, or surgery. The timing of administration and routes are variable and may be critical in determining whether a positive response results.
Certain imidazo[4,5-f]quinolines are known, and it has been disclosed that some of these compounds have antibacterial or anthelminitic activity. The following references disclose certain imidazo[4,5-f]quinolines and methods of synthesizing them and are hereby incorporated by reference: U.S. Pat. No. 3,868,378 issued to Spencer and Alaimo on Feb. 25, 1975; U.S. Pat. No. 3,878,206 issued to Spencer and Snyder on Apr. 15, 1975; U.S. Pat. No. 3,919,238 issued to Spencer and Snyder on Nov. 11, 1975; Ishiwata, S., and Y. Shiokawa, "Synthesis of Benzimidazoles and Related Compounds. II. Syntheses of 3H-Imidazo[4,5-f]- and 1H-Imidazo-[5,4-g]quinolines", Chemical Pharmaceutical Bulletin, Vol. 17 (1969), pp. 2455-2460; Spencer, C. F. , H. R. Snyder, Jr., and R. J. Alaimo, "9-Chloro-(or hydroxy)-2 and/or 7-substituted-imidazo[4,5-f]quinolines (1)", Journal of Heterocyclic Chemistry, Vol. 12, No. 6(December, 1975), pp. 1319-1321; Spencer, C. F., H. R. Synder, Jr., H. A. Burch, and C. J. Hatton, "Imidazo[4,5-f]quinolines. 2. A Series of 9-(Substituted amino)imidazo[4,5-f]quinolines as Antitapeworm Agents", Journal of Medicinal Chemistry, Vol. 20, No. 6 (1977), pp. 829-833; Snyder, H. R., Jr., C. F. Spencer, and R. Freedman, "Imidazo[4,5-f]quinolines III: Antibacterial 7-methyl-9-(substituted Arylamino)imidazo[4,5-f]quinolines", Journal of Pharmaceutical Sciences, Vol. 66, No. 8 (August 1977), pp. 1204-1206; Alaimo, R. J., C. F. Spencer, J. B. Scheffer, R. J. Storrin, C. J. Hatton, and R. E. Kohls, "Imidazo[4,5-f]quinolines. 4. Synthesis and Anthelmintic Activity of a Series of Imidazo[4,5-f]quinolin-9-ols", Journal of Medicinal Chemistry, Vol. 21, No. 3 (1978), pp. 298-300.